Effects of cysteamine and cystamine on the sonochemical accumulation of hydrogen peroxide—implications for their mechanisms of action in ultrasound-exposed cells

Based on the observed cytoprotective effect of the intracellularly permeable radical scavenger cysteamine (+NH3CH2CH2SH) in cells exposed to ultrasound and the lack of protection by its oxidized cell-nonpermeable form, cystamine (+NH3CH2CH2S-SCH2CH2NH3+), it was suggested that inertial cavitation (the growth of small gas bubbles present in the liquid exposed to ultrasound and their subsequent violent collapse) and associated free radical production may occur intracellularly (Radiat. Res. 89:369; 1982). Here we demonstrate that high concentrations (> 10 mM) of the thiol cysteamine effectively lower H2O2 yields following ultrasound exposure in argon- and air-saturated phosphate buffered saline (PBS), while cystamine is less effective under argon and practically without effect in air-saturated PBS. Direct removal of H2O2 by cysteamine is the dominant mechanism while scavenging of the H2O2 precursors √OH and superoxide plays a lesser role. Since H2O2 is a known cytotoxic species capable of penetrating cells if produced extracellularly, these results offer an alternative hypothesis for the protective effect of cysteamine and the lack of protection by cystamine, based on their differential ability to lower ultrasound-dependent H2O2 yields, without the necessity of invoking intracellular cavitation.